BackgroundRecent studies have shown that gastrokine 1 (GKN1), an important tumor suppressor gene, is downregulated in Helicobacter pylori (H. pylori) infected gastric mucosa and gastric cancer. However, the underlying mechanism is poorly understood. Herein, we investigated the potential mechanism of H. pylori‐induced GKN1 downregulation.Materials and methodsGKN1 and AU‐rich element RNA‐binding factor 1 (AUF1) expressions were assessed by quantitative real‐time PCR, Western blot, or immunohistochemistry in H. pylori‐infected tissues and H. pylori co‐cultured cell lines. The regulation of AUF1 on GKN1 was determined by RNA pulldown assay, RNA immunoprecipitation, mRNA turnover, and luciferase activity assays. The involvement of phosphorylated extra‐cellular signal‐regulated kinase (p‐ERK) or CagA in H. pylori‐induced AUF1 expression was verified using p‐ERK inhibitor or CagA knockout H. pylori. In addition, the cell proliferation and migration capacities of AUF1‐knockdown cells were investigated.ResultsGKN1 expression progressively decreased from H. pylori‐infected gastritis to gastric cancer tissues. H. pylori co‐culture also induced significant GKN1 reduction in GES‐1 and BGC‐823 cells. Besides, the mRNA level of GKN1 and AUF1 in human gastric mucosa showed negative correlation significantly. AUF1 knockdown resulted in upregulation of GKN1 expression and promoted GKN1 mRNA decay by binding the 3′ untranslated region of GKN1 mRNA H. pylori‐induced AUF1 expression was associated with p‐ERK activation and CagA. Furthermore, knockdown of AUF1 significantly inhibited cell viability, migration ability, and arrested fewer cells in S‐phase.ConclusionOur data demonstrated that H. pylori infection downregulated GKN1 expression via the CagA/p‐ERK/AUF1 pathway. AUF1 promoted gastric cancer at least partly through downregulating GKN1, which presented a novel potential target for the treatment of gastric cancer.

Helicobacter pylori is a major cause of gastric cancer. This study was aimed to explore the characteristic of DNA damage induced by H. pylori infection in gastric cancer AGS cells. After infection with H. pylori, the reactive oxygen species (ROS) levels in AGS cells were significantly higher than those in the uninfected cells. Cells with longer comet tails were detected after infection with H. pylori. The number of apurinic/apyrimidinic endonuclease 1- and phosphorylated H2AX-positive cells was significantly increased compared with the number of negative control cells. The expression of pChk1 and pChk2 was significantly upregulated by H. pylori infection. Cell growth was inhibited after H. pylori infection. All these results were dose dependent. The cell alterations were more significant upon infection with H. pylori at a multiplicity of infection (MOI) of 100:1 than at an MOI of 50:1. H. pylori infection can induce DNA single-strand breaks, DNA double-strand breaks, and cell cycle checkpoint activation after ROS generation in the gastric cancer cell line AGS, which is a potential driver for gastric cancer.

Background and objective Gastric cancer is one of the most common cancers worldwide. However, the mechanisms associated with this disease are still not clear. Malic enzyme 1 (ME1) is a metabolic enzyme that is overexpressed in various cancers. Here, we examined whether it is involved in gastric cancer. Methods ME1 expression was knocked down in the gastric cancer cell line SGC7901. Cell growth and migration were measured using a real-time microelectronic cell sensor system. Cell invasion was measured using a Transwell assay. Cell cycle analysis was also performed to examine cell cycle arrest. A gastric cancer tissue microarray of gastric cancer was stained using immunohistochemistry. ME1 expression levels were also statistically analysed. Results ME1 knockdown in gastric cancer SGC7901 cells significantly inhibited cell proliferation, migration, and invasion. Cell cycle arrest was induced in the G2 phase. Further, ME1 expression was significantly correlated with gastric cancer patient prognosis based on both univariable and multivariable survival analysis. No significant difference was found between ME1 expression in gastric cancer tissues and that in adjacent tissues. Conclusion Our results provide evidence that ME1 is a key factor for gastric cancer. ME1 might be pro-oncogenic during both the development and migration of gastric cancer; it also might be related to gastric cancer patient survival.

hydrotalcite can protect gastric cells from H. pylori infection when cell damage is not serious. It can weaken the damage of cells induced by H. pylori and decrease H. pylori adhesion to gastric cells.

Background. Recent studies have shown that CagA is considered highly pathogenic to helicobacter pylori (HP) in Western populations. However, in East Asia, CagA positive HP can be up to 90%, but not all patients will lead to gastric cancer. Our research group has found that HP thioredoxin1 (Trx1) may be a marker of high pathogenicity. Here, we investigate whether HP Trx1 exerts high pathogenicity and its internal molecular mechanism. Materials and Methods. We constructed the coculture system of high-Trx1 HP and low-Trx1 HP strains with gastric epithelial cell lines separately and detected the influence of HP strains. The cells were stained by AM/PI, and the cell’s mortality was assessed by fluorescence microscope. The cell’s supernatants or precipitates were collected to detect the expression of IL6. In addition, the cell’s precipitates were collected, and the expression of p-STAT3 was detected by western blot. Furthermore, the cell’s supernatants were collected for detecting the expression of 8-OHDG to investigate the extent of DNA damage. Results. The high-Trx1 HP can cause higher mortality of GES-1 cells compared with the low-Trx1 HP group (high-Trx1 HP ( 4.53 ± 0.56 ) %, low-Trx1 HP ( 0.39 ± 0.10 ) %, P < 0.001 ). The mRNA and protein level of IL-6 in AGS and GES-1 cells were increased during HP infection, and the expression of IL-6 in the High-Trx1 HP group was much higher than the low-Trx1 HP group. Besides, the expression of p-STAT3 was higher in the HP-positive gastric mucosa. And the expression of p-STAT3 in the high-Trx1 HP group was significantly upregulated compared with the low-Trx1 HP group. Furthermore, the expression of 8-OHDG in the high-Trx1 group was much higher than the low-Trx1 group (high-Trx1 HP ( 5.47 ± 1.73 ) ng/ml, low-Trx1 HP ( 2.89 ± 1.72 ) ng/ml, P < 0.05 ). Conclusion. HP Trx1 may play as a marker of high pathogenicity, and the high-Trx1 HP could mediate the pathogenic process of HP infection via the IL6/STAT3 pathway.